Speaker: Shaojun (Jim) Du, Ph.D., Professor of Biochemistry and Molecular Biology, University of Maryland, School of Medicine.
About the speaker: Dr. Du holds a Ph.D. in molecular biology and biochemistry from the University of Toronto and completed postdoctoral training in developmental biology and genetics at the University of Washington. He began his academic career in 1997 at the University of Maryland Biotechnology Institute and became an Associate Professor in 2003. In 2010, Dr. Du joined the University of Maryland Baltimore and now serves as a professor in the Department of Biochemistry and Molecular Biology at the University of Maryland School of Medicine. Learn more
About the seminar: Muscle fibers contain large subcellular assemblies of myofibrils, which are formed by repetitive structures called sarcomeres – the contractile units of muscle cells. Our previous studies have demonstrated that Smyd1 is essential for sarcomere formation in skeletal and cardiac muscles. Loss of Smyd1 results in a complete disruption of sarcomere organization and a dramatic reduction in myosin protein levels in zebrafish embryos. To investigate the molecular mechanisms of Smyd1 function, we characterized gene expression changes in smyd1 knockdown and knockout zebrafish embryos using RNA sequencing (RNA-seq). The results showed that loss of Smyd1 function leads to a dramatic, muscle-specific upregulation of heat shock gene (HSP) expression. The most highly upregulated genes encode cytosolic heat shock proteins involved in proteotoxic stress response. To further investigate the heat shock response and its functional significance in muscle cells, we generated heat shock factor 1 (hsf1) knockout zebrafish mutants and analyzed HSP gene expression and muscle phenotypes in hsf1-/-;smyd1b-/- double mutant embryos. The results showed that hsf1 knockout blocked hsp gene upregulation and exacerbated muscle defects in the double mutants. Moreover, we demonstrated that Hsf1 is essential for zebrafish survival under heat shock conditions. Together, these studies reveal a critical link between Smyd1 deficiency and Hsf1-activated heat shock response in regulating muscle protein homeostasis and myofibril assembly. Furthermore, they demonstrate that Hsf1-mediated HSP gene upregulation is vital for the survival of zebrafish larvae under thermal stress conditions.